Platelet-activating factor (PAF) has been associated with various biological activities and pathways, thus making it an important mediator responsible for a variety of physiological processes, including activation of platelets, smooth muscle contraction, pathogenesis of immune complex deposition, inflammation, and respiratory, cardiovascular and intravascular alterations. These physiological processes are associated with a large group of diseases, such as cardiovascular disorders, asthma, lung edema, endotoxin shock, adult respiratory distress syndrome and inflammatory diseases.
Various classes of compounds are known for inhibiting platelet activation induced by agents such as arachidonic acid, collagen and platelet activating factor. For example, several classes of imidazole derivatives are known for use in treatment of various cardiovascular and immuno-response diseases related to platelet dysfunction or platelet hyperactivity. U.S. Pat. No. 2,025,946 to Iizuki et al mentions certain classes of imidazoles, namely, N-(.omega.-substituted alkylphenylalkyl)imidazoles, N-(.omega.-substituted alkylphenyl)imidazoles and N-(nucleus-substituted phenylakyl)imidazoles which are described as having inhibitory effect on thromboxane synthetase and to be useful for treatment of inflammation, thrombus and asthma. U.S. Pat. Nos. 4,284,641 and 4,416,895 to Thorogood describe certain cycloalkyl/cycloalkenyl imidazoles which inhibit platelet aggregation or reduce the adhesive character of platelets by selective inhibition of thromboxane A2. Also described for the same purpose in U.S. Pat. No. 4,537,340 to Thorogood is a class of 1-arylalkylimidazoles. In U.S. Pat. No. 4,243,671 to Harris et al, the compound 1-(3-phenyl-2-propenyl)1H-imidazole is described as effective in inhibiting thromboxane synthetase, arachidonic acid-induced platelet aggregation and bronchoconstriction.
Compounds are known for use in treating platelet dysfunction or platelet hyperactivity induced specifically by platelet activating factor (PAF). For example, a certain class of glycerol derivatives useful as PAF antagonists is described in EP No. 142,333. A class of indene derivatives is described in EP No. 142,801 as PAF inhibitors. Compounds containing heterocyclic moieties of various types are also known as PAF antagonists. For example, U.S. Pat. No. 4,579,862 to Manley et al describes certain imidazole/pyridinylalkanoic acid derivatives as PAF antagonists. U.S. Pat. No. 4,804,658 to Manley et al describes a class of imidazopyridine derivatives useful as PAF inhibitors and mentions, in particular, the compound N-cyclohexyl-N-methyl-4-(1H-imidazo [4,5-c]pyridin-1-yl-methyl)benzamide as an inhibitor of PAF-induced aggregation in an assay using human platelet-rich plasma. U.S. Pat. No. 4,914,108 to Khanna et al describes a class of 5-substituted(4,5-c) imidazopyridine compounds having PAF antagonist activity, including, in particular, the compound 5-[4{-(N-isopropyl,N-cyclohexyl)carboxamido}-2-methoxybenzyl]imidazo[4,5-c ]pyridine.